Project Summary Alcohol Use Disorder (AUD) is a chronic brain disease with major health and societal concerns resulting in more deaths than any other type substance misuse. Of all the forms of alcohol misuse, binge drinking is the most common, costly, and deadly pattern of excessive alcohol use. Addressing this major public health problem requires a better understanding of the underlying neurobiology of binge drinking. One region of particular interest for binge-drinking is the prelimbic cortex (PL). We have previously shown that excitatory and inhibitory signaling in the PL is altered following a variety of models of ethanol exposure. In addition, our preliminary data indicates that somatostatin neurons in the PL are involved in alcohol binge drinking in both sexes. This is particularly novel as it represents a promising neuronal population capable of reducing binge drinking behavior. Our project will (1) investigate how PL somatostatin neurons interact with other neurons (synaptic connectivity and signaling), and (2) what role they play in binge drinking (chemogenetic activation and inhibition). Taken together, these experiments will assess the hypothesis that somatostatin neurons in the PL are a promising therapeutic target for alcohol use disorder, and binge drinking in particular.